Nature - A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic
The COVID-19 pandemic caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced due to emerging variants of concern . Development of host-directed therapeutics and prophylactics could limit such resistance and offer urgently needed protection against VOCs.
Here, we identify and characterize a small-molecule compound, N-0385, which exhibits low nanomolar potency and a selectivity index of >10. In Calu-3 cells it inhibits entry of SARS-CoV-2 VOCs, B.1.1.7, B.1.351, P.1 and B.1.617.2. Importantly, in the K18-human ACE2 transgenic mouse model of severe SARS-CoV-2 disease, we found that N-0385 affords a high level of prophylactic and therapeutic benefit following either multiple or even a single administration.
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